Certain pharmaceutically active ingredients, such as analgesics, must be employed in relatively high doses to be therapeutically effective. Acetaminophen, for example, is commonly used at 1000 mg per dose, divided into two tablets containing 500 mg each. Formulating high levels of an active ingredient into a tablet that remains small enough for a consumer to swallow comfortably is a challenge. This is complicated by the fact that most active ingredients will not by themselves readily compress into a tablet. Accordingly, they are mixed with inactive excipients that form bonds under compression to hold the tablet together. One common method of accomplishing this is by wet granulation, in which the active ingredient and an aqueous solution of a binder (such as starch paste) are mixed and granulated. The resulting material is suitable for compression into tablets.
More recently, direct compression of dry blends has gained favor in the pharmaceutical industry due to the economics of eliminating wet granulation and its accompanying drying operations. Direct compression is useful for active ingredients that are highly potent. However, the relatively high amount of low potency active ingredients required in a dosage form makes them poor candidates for direct compression into tablets.
Workers in the field have attempted to overcome this problem. For example, U.S. Pat. Nos. 4,661,521 and 4,757,090 to Salpekar et al. relate to an N-acetyl-p-aminophenol (acetaminophen) composition capable of being directly formed into a tablet, comprising acetaminophen, a pharmaceutically acceptable pregelatinized starch, a pharmaceutically acceptable lubricant, water and optionally an auxiliary binder such as polyvinylpyrrolidone. These compositions are prepared by wet granulation using an aqueous starch slurry.
U.S. Pat. No. 4,882,167 to Jang describes a controlled and continuous release matrix for tablets or implants of biologically active agents. The matrix comprises a hydrophobic carbohydrate polymer such as ethyl cellulose, and optionally at least one digestive-difficulty soluble component such as wax, fatty acid material or a neutral lipid.
U.S. Pat. No. 5,169,645 to Shukla et al. relates to directly compressible, wax-containing granules useful as a particulate drug diluent. The granules are made by admixing in the melted state one or more pharmaceutically acceptable waxes with one or more flow improving additives, cooling the mixture and then granulating. The resulting wax-containing granules can be compressed into matrices containing an active ingredient.
PCT Application WO 99/32092 discloses a method for the manufacture of tablets that disperse easily and quickly in the oral cavity. The method comprises preparing a dry granulation of one or more medicaments blended with suitable excipients, flavors and a combination of a waxy material and phospholipid or an intense sweetener for taste-masking and compressing into tablets. The resulting tablets comprise 1 to 60 parts of the medicament.
U.S. Pat. No. 5,456,920 to Matoba et al. describes a compression-moldable composition comprising an active ingredient, an excipient, and an oily or fatty substance having a lower melting point of about 20° to 90° C.
It has now been discovered that an immediate release tablet can be made from a mixture comprising at least 60 weight % active ingredient(s) and a powdered wax having a melting point of greater than about 90° C. Although the powdered wax is hydrophobic, the tablets have excellent disintegration, and meet the USP dissolution specifications for immediate release tablets containing the active ingredient. Rapid onset of therapeutic action is a desirable feature, especially for analgesics.